不完全外显的遗传性痉挛性截瘫一家系临床与致病基因排除定位分析

The clinical characteristics of a pedigree with incompletely penetrated autosomal dominant hereditary spastic paraplegia and its exclusion analysis of genetic loci

目的描述一个遗传了4代的不完全外显的遗传性痉挛性截瘫（hereditary spastic paraplegia，SPG）大家系的临床特征，并进行致病基因排除定位分析。方法对SPG家系内11例患者的临床资料进行回顾性分析，并采用荧光多重PCR、毛细管凝胶电泳、Linkage软件包，选择对已定位常染色体显性遗传致病基因位点附近微卫星标记进行连锁分析。结果该SPG家系的11例患者的发病年龄2～10岁，表现为缓慢进展的双下肢僵硬无力，四肢肌张力轻度增高，双上肢为主的腱反射亢进，剪刀步态和病理征阳性，无小便失禁或尿频、感觉障碍、眼震、痴呆等；遗传学分析该家系符合常染色体显性遗传，但外显不完全，连锁分析和突变分析发现该家系与已知的常染色体显性遗传SPG致病基因位点不连锁。结论该SPG家系具有典型的“单纯型”痉挛性截瘫临床特点，发病年龄早，上肢体征较下肢明显，遗传学分析不支持该家系与已定位常染色体显性遗传位点相连锁，是一种新的SPG亚型。

Objective To describe the clinical features of a big family with incompletely penetrated autosomal dominant hereditary spastic paraplegia （SPG） and perform the exclusion analysis of genetic loci. Methods The ehnieal information of this SPG family was analyzed retrospectively. Exclusion analysis of the known autosomal dominant SPG loci was performed by using multiplex fluorescence PCR, capillary eleetmphoresis and Linkage package. Results There were eleven affected members available in this SPG family and the age at onset ranged from 2 to 10 years. The first symptoms were a bilateral, symmetrical, progressive lower limb weakness and spastieity. Patients presented with spastieity and hyperreflexia, positive Babiuski sign and scissors gait, and the upper limbs were involved more severely than the lower limbs. No urinary inconsistence, sensory impairment, nystngmus and dementia were found. Genetic analysis showed that this family was consistent with autosomal dominant inheritance. The linkage analysis and mutation analysis revealed this family was not linked to the known autosomal dominant loci. Conclusion This SPG family had typical ＂pure＂ clinical symptoms. The age at onset was early and the signs in the upper limbs were more obvious than those in the lower limbs. The result of linkage analysis shows that this family represents a new SPG subtype.